Rapid and real-time detection of chemical, biological and explosive agents without the need for elaborate laboratory facilities is desirable for many applications, including, for example, medical and security applications. Optical sensing technologies have been used for detecting agents in various fluids. Optical sensing technologies generally use an optical probe beam to interact with a material to be detected. Some aspect of the optical probe beam is modified by this interaction between the optical probe and the material. A portion of this modified beam, such as the scattered light, the reflected light, or the transmitted light, may be collected and measured to obtain certain information of the material. Under proper conditions, optical sensing is a non-invasive technique that does not materially alter the contents under measurement/test. The spectrum of a probe beam may be controlled to selectively interact with specified particles, molecules, or atoms in the material to elicit some measurable modifications in the optical beam, wherein the modifications are indicative of the identity of the material constituents. Optical sensing may also be used for applications requiring high sensitivity and/or detection of minute amounts of a particular material.
Certain known optical sensors, such as single molecule sensors, typically require a fluorescent or metallic label attached to the target molecule so that the target molecule may be identified. Such labels, however, require prior knowledge of the presence of the target molecule(s). Thus, current sensing systems that require labels are not suitable for blind detection of target molecules, which do not have labels. Labels can structurally and/or functionally interfere with an assay, or may not be specific or be difficult to conjugate. Such problems are often encountered in single molecule experiments. Furthermore, such labels may require additional data processing. For example, sensors using labels may require ensemble averaging of large numbers of cells, resulting in confusion or dulling of recorded responses in those cases in which there is heterogeneity in the cells or their responses. Current methods of detection using labels cannot be performed in real-time.
Several devices have been used for label-free detection. Such devices include fiber optic waveguides, nanowires, nanoparticle probes, biochips, mechanical cantilevers, micro-sphere resonators, and Quartz Crystal Modulator (QCM) oscillators, as well as acousto/optical and acoustic wave devices. While certain known devices may provide label-free detection, such devices have significant drawbacks. For example, various known sensors lack sufficient sensitivity to enable detection of a very small number of molecules or a single molecule, and therefore, prove unsuitable for biological and chemical analyses requiring more specific detection, such as cell signaling and cellular dynamics. Previous experiments with silica micro-spheres, for example, demonstrated gross detection of approximately 1 billion molecules. Such devices are not suitable for detection of a very small number of molecules or a single molecule.
Sensitivities of sensors having mechanical components may be limited by the sensitivities that can be achieved given the particular mechanical construct. Furthermore, such devices are often subject to electromagnetic interference. In the case of certain optical sensors and traps, sensitivity limitations are due, in part, to the limited interaction of light with the target molecule. For example, in a simple optical waveguide sensor, the input light has only one opportunity to interact with the target molecule. Accordingly, blind, real-time, and label-free molecule detection methods and sensor systems having enhanced specificity and sensitivity for detecting very small numbers of molecules or for single molecule detection are desirable.